Abstract PR07: Synchronous ovarian and endometrial carcinomas: The case for pseudo-metastasis.

Abstract

Background: Almost half of ovarian endometrioid histotype carcinomas present with concurrent endometrial carcinoma or pre-cancerous lesions. These “synchronous” ovarian and endometrial (SEO) tumors, when organ-confined and low-grade, consistently behave as two independent primary tumors, rather than a tumor-metastasis pair typical of advanced-stage carcinoma. Our study aims to investigate the ancestral relationship between ovarian and endometrial components of SEOs. Methods: We identified a cohort of SEOs and performed targeted, with the Illumina Truseq Custom Amplicon assay, and exome-level, with Nugen Ovation Library System and Agilent SureSelect XT2 capture, library construction followed by massively parallel sequencing on illumina MiSeq or HiSeq. Results: Despite complexities introduced as a result of sampling formalin fixed and paraffin embedded archival specimens we were able to confirm shared identical mutations, and thus a clonal relationship, between ovarian and endometrial tumors in all but one case. Discussion: In simultaneous presentation of cancer of the endometrium and ovary from our series we observed strong evidence of a primary tumor and metastasis relationship. However, the clinical behavior of this series, and SEOs in general, defies the basic tenant of cancer metastasis as a dire prognosis. Curiously similar anomalies, where there is advanced stage yet favorable outcome, occur in other organ systems. We therefore suggest a generalizable process “pseudo-metastasis” through which cells can spread to microenvironment-compatible and physically accessible sites. This restricted metastatic process can occur in cells that lack the full complement of cancer-associated transformation hallmarks required for tissue invasion and hematogenous or lymphatic metastasis. This phenomenon may be an important early step in dissemination of apparent multi-focal benign lesions, pre-malignant lesions, and low-grade carcinomas. This abstract is also presented as Poster B07. Citation Format: Michael S. Anglesio, Yi Kan Wang, Madlen Maassen, Hugo M. Horlings, Ali Bashashati, Blake Gilks, Stefan Kommoss, David G. Huntsman. Synchronous ovarian and endometrial carcinomas: The case for pseudo-metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr PR07.

LINE-1 retrotransposon-mediated DNA transductions in endometriosis associated ovarian cancers

“…We also found somatic mutations and TTC28-L1 events shared between the uterine and ovarian tumors in ENOC 2 and ENOC 4, however, we did not detect any of our selected mutations nor the TTC28-L1 event in the uterine tumor from CCOC 3. CCOC 3 was unusual in several ways: different pathologies observed in the ovary (clear cell) and uterus (endometrioid), and there was only one single shared somatic event (a different event from the ones we repeated) as reported by Anglesio et al [23]. It is possible this somatic event had occurred before either the seeding of endometriosis or the activation of the TTC28-L1 retrotransposon.…”

“…Targeted resequencing was previously used by our group to describe a clonal relationship between the endometrial and ovarian cancers in three of the four synchronous endometrioid and ovarian tumors, ENOC 2, ENOC 4 and CCOC 3 [23]. We also found somatic mutations and TTC28-L1 events shared between the uterine and ovarian tumors in ENOC 2 and ENOC 4, however, we did not detect any of our selected mutations nor the TTC28-L1 event in the uterine tumor from CCOC 3.…”

Molecular analysis suggests oligoclonality and metastasis of endometriosis lesions across anatomically defined subtypes

“…Thus, OMAs with multiple PIK3CA mutant clones may have elevated malignant potential. In contrast, the extraovarian microenvironment restriction on malignant potential has been suggested as a potential mechanism for the generally favorable outcomes observed in low-stage synchronous (yet metastatic) endometrioid ovarian and endometrial carcinomas (43).…”